article
Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets
Registro en:
Juan D. Cortés-Garcia, Cintya López-López, Nancy Cortez-Espinosa, Mariana H. García-Hernández, Juan M. Guzmán-Flores, Esther Layseca-Espinosa, Liliana Portales-Cervantes, Diana P. Portales-Pérez, Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets, Immunobiology, Volume 221, Issue 1,
2016, Pages 84-93.
Autor
Cortés García, Juan Diego
López López, Cintya del Refugio
Cortez Espinosa, Nancy
García Hernández, Mariana Haydee
Guzman-Flores, Juan Manuel
Layseca Espinosa, Esther
Portales Cervantes, Liliana
Portales Pérez, Diana Patricia
Resumen
"Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis. However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore, NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and cause cell depletion in murine models. We evaluated the expression and function of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7 and ART1 expression was assessed by flow cytometry and real-time PCR. Our results showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1 expression in CD4+ CD39+ T cells than the other subtypes studied. Neither shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed by 1mM ATP or 60 mu M NAD. In contrast, P2Xs receptor-dependent proliferation with 300 p,M ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2X5 and A2a agonist and was reversed with P2X5 and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation and A2a activation. In conclusion, our results suggest that the altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39 Treg cells could participate in the resistance against cell death induced by ATP or NAD. (C) 2015 Elsevier GmbH. All rights reserved."